The mechanism by which heme and hemoproteins are converted to bile pigments will be investigated by synthesizing probable intermediates and studying their metabolism by hepatic microsomes and parenchymal cells in vitro and by rats in vivo. The structural requirements of the active site of the heme-cleaving enzyme system will be elucidated by detailed studies of the non-enzymatic coupled-oxidation of hemoproteins to bile pigments. Experiments to determine the mechanism of phototherapy will be carried out using the Gunn rat as an animal model. Photoproducts of bilirubin formed in vivo will be isolated and identified and the kinetics and sites of action of phototherapy will be determined. These studies will provide information which will be important in assessing the safety of phototherapy of newborn infants with hyperbilirubinemia and may lead to improvements in the effectiveness of this treatment.